Placental DNA hypomethylation in association with particulate air pollution in early life

Abstract

BackgroundThere is evidence that altered DNA methylation is an important epigenetic mechanism in prenatal programming and that developmental periods are sensitive to environmental stressors. We hypothesized that exposure to fine particles (PM2.5) during pregnancy could influence DNA methylation patterns of the placenta.MethodsIn the ENVIRONAGE birth cohort, levels of 5’-methyl-deoxycytidine (5-mdC) and deoxycytidine (dC) were quantified in placental DNA from 240 newborns. Multiple regression models were used to study placental global DNA methylation and in utero exposure to PM2.5 over various time windows during pregnancy.ResultsPM2.5 exposure during pregnancy averaged (25th-75th percentile) 17.4 (15.4-19.3) μg/m3. Placental global DNA methylation was inversely associated with PM2.5 exposures during whole pregnancy and relatively decreased by 2.19% (95% confidence interval [CI]: -3.65, -0.73%, p = 0.004) for each 5 μg/m3 increase in exposure to PM2.5. In a multi-lag model in which all three trimester exposures were fitted as independent variables in the same regression model, only exposure to PM2.5 during trimester 1 was significantly associated with lower global DNA methylation (-2.13% per 5 μg/m3 increase, 95% CI: -3.71, -0.54%, p = 0.009). When we analyzed shorter time windows of exposure within trimester 1, we observed a lower placental DNA methylation at birth during all implantation stages but exposure during the implantation range (6-21d) was strongest associated (-1.08% per 5 μg/m3 increase, 95% CI: -1.80, -0.36%, p = 0.004).ConclusionsWe observed a lower degree of placental global DNA methylation in association with exposure to particulate air pollution in early pregnancy, including the critical stages of implantation. Future studies should elucidate genome-wide and gene-specific methylation patterns in placental tissue that could link particulate exposure during in utero life and early epigenetic modulations.

Placental mitochondrial methylation and exposure to airborne particulate matter in the early life environment: An ENVIRONAGE birth cohort study

“…29 Epigenetic modifications represent a potential link between adverse insults and altered fetal development. Previously, we have shown that PM 2.5 exposure during pregnancy affects global DNA methylation levels in placental tissue, 30 while in this study, we investigated the impact of PM 2.5 exposure upon epigenetics of placental mitochondria. Using the bisulfite-pyrosequencing approach, we were able to detect subtle differences in methylation levels of specific regions in the mitochondrial genome (Fig.…”

“…As described previously, 30 we took villous tissue (1 to 2 cm 3 ) at a fixed location from the fetal side of the placenta, approximately 1-1.5 cm below the chorio-amniotic membrane, and preserved the biopsies at -80 C. Chorio-amniotic membrane contamination was avoided by careful visual examination and dissection.…”

Air Pollution and Epigenetics: Recent Findings

“…While all of the above studies were conducted in adults, previous research suggests that early developmental periods are particularly vulnerable to epigenetic dysregulation in response to environmental exposures [18,34]. Both human and animal models of prenatal exposure provide evidence that increased DNA adducts and global hypomethylation induce genomic and chromosomal instability [18,34].…”

Preconception and Prenatal Factors and Metabolic Risk

“…Both animal models and human studies implicate the intrauterine period as a sensitive time for the establishment of epigenetic variability (Heijmans et al 2008;Cook et al 2007;Tang et al 2012;Radford et al 2014;Janssen et al 2013), which in turn influences risk for a range of disorders that develop later in life. In the Boston Birth Cohort, we observed a wide range of interindividual variations in genome-wide methylation at birth (Wang et al 2012).…”